Breast cancer kills thousands of women annually. While surgical intervention has saved the lives of many women, radical and partial mastectomies often prove physically and emotionally debilitating. Moreover, patients who have undergone surgery and subsequent chemotherapy often experience recurrence.
The 4H-1-benzopyran-4-one ring system is widely found in a number of natural products such as flavonoids. These natural products have demonstrated numerous biological activities such as antiviral, anti-inflammatory, antiallergic, antimutagenic and anticarcinogenic activities.1 Genistein, an isoflavonoid, for example, has been known to act as an antagonist on the estrogen receptor suppressing the development of hormone-dependent breast cancer.
This fact has led us to investigate novel 4H-1-benzopyran-4-one derivatives as new therapeutic agents for hormone-dependent breast cancer.2 As part of this effort, we have been interested in 3-aryl-2-alkylthio-4H-1-benzopyran-4-ones, or 2-(alkylthio)isoflavones, as potential drug candidates in this area. However, only a few methods have been reported for the synthesis of 2-alkylthio-4H-1-benzopyran-4-ones.3 Furthermore, these methods suffer several disadvantages such as low yields, multiple steps, and harsh conditions. Recently, a high yielding one-pot synthesis of 2-methylthio-4H-1-benzopyranones has been reported using KHMDS as a base.4 However, this method also requires skillful handling of the base, low temperature, and anhydrous reaction conditions. A convenient method of synthesis of 2-alkylthio-4H-1-benzopyran-4-ones or 2-(alkylthio)isoflavones would provide a convenient starting point for the development of new therapeutics for the treatment of breast cancer.
Accordingly, it is desirable to have new compounds and methods for the treatment of hormone dependent breast cancer, as well as other cancers. It is also desirable to have new, efficient, methods for the syntheses of these new compounds. It is particularly desirable that these new synthetic methods have few steps, improved yields, and mild conditions.